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Purpose: In this study, we investigated the effects of different concentration of propofol on cell viability of hippocampal neurons and explored the possible mechanism. Patients and methods: Primary hippocampal neurons were cultured in vitro and treated with different concentration of propofol. MTT was used to examine the survival of neurons. Flow cytometry was used to detect the neuronal apoptosis. Western-blot analysis was used to examine the expression level of p-p38MAPK and p38MAPK. Results: We found that low concentration propofol (0.5 μM and 1 μM) promoted the cell survival rate; however, high concentration of propofol (10 μM,50 μM,100 μM,150 μM, and 200 μM) decreased the cell survival rate (P < 0.05). Flow cytometry showed that the neuronal apoptosis rate was decreased in 1 μM propofol group (P < 0.05), but was significantly higher in10μM, 100 μM and 200 μM groups in a concentration-dependent manner (P < 0.05 or P < 0.01). Western blot revealed that the propofol induced the phosphorylation of p38MAPK concentration-dependently and time-dependently. SB203580, one inhibitor of p38MAPK, increased the cell survival rate and decreased the cell apoptosis induced by high concentration of propofol. Conclusion: Low concentration of propofol improved the survival rate of neurons, while high concentration of propofol promoted the cell apoptosis and decreased the cell viability. p38MAPK pathway is involved the effect of high concentration of propofol promoted on primary hippocampal neurons viability and apoptosis. [ABSTRACT FROM AUTHOR]